ABSTRACT
ACE2, the first known human homologue of angiotensin-converting enzyme (ACE), was identified from 5' sequencing of a human heart failure ventricle cDNA library. ACE2 has an apparent signal peptide, a single metalloprotease active site, and a transmembrane domain. The metalloprotease catalytic domains of ACE2 and ACE are 42% identical, and comparison of the genomic structures indicates that the two genes arose through duplication. In contrast to the more ubiquitous ACE, ACE2 transcripts are found only in heart, kidney, and testis of 23 human tissues examined. Immunohistochemistry shows ACE2 protein predominantly in the endothelium of coronary and intrarenal vessels and in renal tubular epithelium. Active ACE2 enzyme is secreted from transfected cells by cleavage N-terminal to the transmembrane domain. Recombinant ACE2 hydrolyzes the carboxy terminal leucine from angiotensin I to generate angiotensin 1-9, which is converted to smaller angiotensin peptides by ACE in vitro and by cardiomyocytes in culture. ACE2 can also cleave des-Arg bradykinin and neurotensin but not bradykinin or 15 other vasoactive and hormonal peptides tested. ACE2 is not inhibited by lisinopril or captopril. The organ- and cell-specific expression of ACE2 and its unique cleavage of key vasoactive peptides suggest an essential role for ACE2 in the local renin-angiotensin system of the heart and kidney. The full text of this article is available at http://www. circresaha.org.
Subject(s)
Angiotensin I/metabolism , Carboxypeptidases/genetics , Kidney/enzymology , Myocardium/enzymology , Renin-Angiotensin System , Adult , Amino Acid Sequence , Angiotensin-Converting Enzyme 2 , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Animals , Base Sequence , CHO Cells , Carboxypeptidases/chemistry , Carboxypeptidases/metabolism , Cardiomyopathy, Dilated/enzymology , Cells, Cultured , Cricetinae , Culture Media, Serum-Free , Female , Gene Duplication , Gene Expression Regulation, Enzymologic , Gene Library , Genetic Vectors , Heart Ventricles/enzymology , Humans , Lisinopril/pharmacology , Male , Mass Spectrometry , Molecular Sequence Data , Myocardium/cytology , Peptidyl-Dipeptidase A/genetics , Sequence Alignment , Sequence Homology, Amino Acid , Substrate Specificity , Testis/enzymology , TransfectionABSTRACT
Resuscitation from clinical cardiac arrest is complex and often takes several years to learn. This paper describes an intelligent simulation-based tutor for ACLS which increases students' opportunity to practice before, during and after the ACLS course, thus bridging the gap between studying theory and didactic textbook material and working with patients. Sophisticated reasoning about student performance, compared to an expert model, distinguishes this system from other computerized instruction systems. Intelligence in the tutor allows the system to make the simulation dynamically adaptive to focus on areas where the student's learning needs are greatest. A formative evaluation with two classes of fourth year medical students suggested that the tutor was helpful, realistic and effective. Positive reactions and strong student involvement with the simulation suggest that this simulation-based tutor may improve learning and retention while decreasing anxiety for most students.
Subject(s)
Computer Simulation , Computer-Assisted Instruction , Heart Arrest/therapy , Resuscitation/education , Education, Medical, Undergraduate/methods , HumansABSTRACT
Prolonged apnoea occurs occasionally after the routine use of suxamethonium chloride (Scoline). A case history is presented where the use of stabilised human serum (SHS) resulted in a dramatic reversal of this problem. Guidelines for the management of this condition with special reference to the use of SHS are discussed.
Subject(s)
Apnea/therapy , Blood Transfusion , Succinylcholine/adverse effects , Adult , Apnea/chemically induced , Cholinesterases/blood , Female , HumansABSTRACT
We trained monkeys to perform visuomotor tracking tasks in which the target's position was unpredictable, or in which the target jumped from one side of the screen to the other ('ballistic'). Section of the right dorsal funiculus at C2 resulted in transient deficits in both tasks, with full recovery of function. Subsequent removal of postcentral cortex in the left hemisphere produced a more intense and stable deficit in performance. We conclude that proprioceptive data on limb position and movement must be able to reach motor command structures by pathways paralleling the dorsal column-medial lemniscus system.
